The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index.
Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells
Open accessAbstract
In the central nervous system (CNS), myelin formation and repair are regulated by oligodendrocyte (OL) lineage cells, which sense and integrate signals from their environment, including from other glial cells and the extracellular matrix (ECM). The signaling pathways that coordinate this complex communication, however, remain poorly understood. The adhesion G protein-coupled receptor ADGRG1 (also known as GPR56) is an evolutionarily conserved regulator of OL development in humans, mice, and zebrafish, although its activating ligand for OL lineage cells is unknown. Here, we report that microglia-derived transglutaminase-2 (TG2) signals to ADGRG1 on OL precursor cells (OPCs) in the presence of the ECM protein laminin and that TG2/laminin-dependent activation of ADGRG1 promotes OPC proliferation. Signaling by TG2/laminin to ADGRG1 on OPCs additionally improves remyelination in two murine models of demyelination. These findings identify a novel glia-to-glia signaling pathway that promotes myelin formation and repair, and suggest new strategies to enhance remyelination.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Furthermore, microglia express factors like Transglutaminase 2, which is essential for OPCs differentiation (13).”
From Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination (2025) · cites this paper as [13]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Among them is Adgrg1 (Gpr56), demonstrated previously to be conserved in human, mouse, and zebrafish, which is associated with development of oligodendrocytes”
From Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program (2019) · cites this paper as Giera et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“Whether this prolonged inflammatory response is beneficial for remyelination remains unclear, but microglia have been previously shown to promote remyelination independent of debris clearance55–57.”
From A comparative transcriptomic analysis of mouse demyelination models and multiple sclerosis lesions (2026) · cites this paper as [55]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Bialas, A. R., & Stevens, B. (2013) · Nature Neuroscience · doi:10.1038/nn.3560 · Cited by 519
Self-citationRetractedZhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245
High-resolution in situ hybridization to whole-mount zebrafish embryos
Thisse, C., & Thisse, B. (2007) · Nature Protocols · doi:10.1038/nprot.2007.514 · Cited by 2,587
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,777
The central nervous system and the gut microbiome
Sharon, G., Sampson, T. R., Geschwind, D. H., & Mazmanian, S. K. (2016) · Cell · doi:10.1016/j.cell.2016.10.027 · Cited by 1,513
Transglutaminases: crosslinking enzymes with pleiotropic functions
Lorand, L., & Graham, R. M. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1014 · Cited by 1,439
Microglia development follows a stepwise program to regulate brain homeostasis
Matcovitch-Natan, O., Winter, D. R., Giladi, A., Vargas Aguilar, S., Spinrad, A., Sarrazin, S., Ben-Yehuda, H., David, E., Zelada González, F., Perrin, P., et al. (2016) · Science · doi:10.1126/science.aad8670 · Cited by 1,180
Myelination of the Nervous System: Mechanisms and Functions
Nave, K.-A., & Werner, H. B. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-013101 · Cited by 983
Oligodendrocyte Dynamics in the Healthy Adult CNS: Evidence for Myelin Remodeling
Young, K. M., Psachoulia, K., Tripathi, R. B., Dunn, S.-J., Cossell, L., Attwell, D., Tohyama, K., & Richardson, W. D. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.006 · Cited by 919
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–146 of 146
Hein, Z. M., Abdelra, A. O. Z. S. A., Shahbaz, S. B. A., & Nassir, C. M. N. C. M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05778-z · Cited by 5
Bauer, L., Edwards, J., Heil, A., Dewitt, S., Biebermann, H., Aeschlimann, D. P., & Knäuper, V. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042329 · Cited by 5
Bandekar, S. J., Dintzner, E. E., Leon, K., Kordon, S. P., Ślężak, T., Cechová, K., Vafabakhsh, R., & Araç, D. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2409184122 · Cited by 5
Zuo, Z., Zhou, H., & Zhou, J. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190717112944 · Cited by 6
Computer program for evaluating coal washer performance
Wizzard, J. T. (1983) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) · Cited by 5
A comparative transcriptomic analysis of mouse demyelination models and multiple sclerosis lesions
Aboelnour, E. L., Vanoverbeke, V. R., Maupin, E. A., Hatfield, M. M., & Adams, K. L. (2026) · Nature Communications · doi:10.1038/s41467-026-72383-y · Cited by 4
Zamberletti, E., Manenti, C., Prini, P., Gabaglio, M., Grimaldi, A., Pulze, L., Grassi, R., & Rubino, T. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107758 · Cited by 4
Remyelinating strategies: What can be learned from normal brain development
Shelestak, J., Irfan, M., & DeSilva, T. M. (2022) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2022.102290 · Cited by 4
Oliveira, N. A. D. J., Lewkowicz, K. R., Clow, P. A., Ward, M. E., Cookson, M., Skarnes, W. C., & McDonough, J. A. (2025) · Bioengineering · doi:10.3390/bioengineering13010045 · Cited by 3
Targeting Neuroinflammation in Depression: The Integrative Role of Sigma‐1 Receptor Modulation
Wang, J., Yang, D., Li, Y., & Ren, P. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70490 · Cited by 3
GPR56 function as a key repressor in hepatocyte pyroptosis and the pathogenesis of liver fibrosis
Shi, Z.-M., Liu, Q., Zhang, M., Du, X.-X., He, Y., Zheng, L., Hong, W., Han, T., & Zhang, K.-W. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06619-8 · Cited by 2
Mechanosensitive adhesion G protein-coupled receptors: Insights from health and disease
Sun, S., & Wang, W. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101267 · Cited by 4
Lion, M., Ibrahim, E. C., Caccomo-Garcia, E., Bourret, J., Cinquanta, G., Khalfallah, O., Glaichenhaus, N., Davidovic, L., Courtet, P., Turecki, G., et al. (2025) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2025.01.001 · Cited by 2
G Protein‐Coupled Receptor Signaling in CNS (Re)Myelination
McDonald, J. K., Ang, S. Y., Langmead, C. J., & Stewart, G. D. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70286 · Cited by 2
The therapeutic potential of orphan adhesion G-protein-coupled receptors
Sun, J., Xiao, P., & Liebscher, I. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01371-6 · Cited by 2
Shaath, R., Al-Maraghi, A., Ali, H., AlRayahi, J., Kennedy, A. D., DeBalsi, K. L., Hussein, S., Elbashir, N., PADMAJEYA, S. S., Palaniswamy, S., et al. (2024) · Metabolites · doi:10.3390/metabo14030152 · Cited by 3
ADGRG1 , an adhesion G protein‐coupled receptor, forms oligomers
Cevheroğlu, O., Demirbaş, B., Öğütcü, D., & Murat, M. (2024) · FEBS Journal · doi:10.1111/febs.17117 · Cited by 2
Linking adhesion GPCRs to glial cell development and function
Chiou, B., & Piao, X. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817986-4.00009-2 · Cited by 1
Self-citationTransglutaminase 2 in neurological conditions
Delgado, T., & Johnson, G. V. W. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19168-8.00005-5 · Cited by 2
Aberle, T., & Wegner, M. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00520 · Cited by 1
Relationship of immune-inflammatory pathway and stress-induced depression with neural regeneration
Yu, Q., Chen, Z., Zhang, J., Cao, Y., Sun, M., Ye, S., Huang, Y., He, J., Wang, L., Li, K., et al. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00324 · Cited by 1
Conserved and lineage-specific mechanisms drive chromatophore differentiation in reptiles
Helleboid, P., & Tzika, A. C. (2026) · Nature Communications · doi:10.1038/s41467-026-75281-5 · Cited by 1
Pre-myelinating oligodendrocyte ADGRG1 is required for axon ensheathment and CNS myelin formationPreprint
Zhu, B., Li, T., Rodrigues, B. V., Piller, M., Call, C. L., Mogha, A., Belloso-Iguerategui, A., Chiou, B., Schmidt, R., Wangzhou, A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.26.701898 · Cited by 1
Self-citationThe Role of GPR56 in Neurofibromatosis type 1 Secondary to ScoliosisPreprint
Cai, S., Yang, Y., Jia, B., Wu, Z., Zhang, J., Shen, J., & Qiu, G. (2020) · doi:10.21203/rs.3.rs-74862/v1
Gliovascular Mechanisms and White Matter Injury in Vascular Cognitive Impairment and Dementia
Rosenberg, G. A., Maki, T., Arai, K., & Lo, E. H. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-69424-7.00013-2
One-shot valve may be remotely actuated
Kami, S. (1965) · NASA STI Repository (National Aeronautics and Space Administration)
Ghosh, M., & Pearse, D. D. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.330598
Xiao, X., Ling, W., Qiu, X., Wang, M., Xiong, C., Xie, D.-F., Chu, X., Li, Y.-X., Huang, Y., Li, T., et al. (2020) · doi:10.21203/rs.3.rs-35533/v1
Human Neocortical Evolution and Neurological Disorders
SeanHill, R., & Walsh, C. A. (2023) · Wiley eBooks · doi:10.1002/9781119860914.ch26
Syage, A. R., Pachow, C., Murray, K. M., Henningfield, C. M., Fernandez, K., Du, A. X., Cheng, Y., Olivarria, G. M., Kawauchi, S., MacGregor, G. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26734428
Iwasawa, E., Brown, F. N., Shula, C., Emmert, A. S., Fugate, E. M., Lindquist, D. M., Mangano, F. T., & Goto, J. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115608
Weber, D. J., Cook, M. E., Yu, W., Redondo, M., & Godoy‐Ruiz, R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27062902
Microglia-nodes of Ranvier interaction during repair
Roux, T. (2020) · theses.fr (ABES) · doi:10.70675/a1319259z2b39z4d4ez9c05z261e4533646b
Pantazou, V., Dorcet, G., Roux, T., Aigrot, M., Perrot, C., Mathias, A., Canales, M., Lejeune, F., Stankoff, B., Pasquier, R. D., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.14.718431
Self-cleavage-dependent and -independent functions of Adgrg1/Gpr56 in mice
Kwarcinski, F. E., Bernadyn, T. F., Teuber, J. P., Nascimento, M. C. F., Bergin, I. L., Shen, T., Gandhi, R., Lu, X., Brody, M. J., Holinstat, M. A., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2527832123
Self-citationG protein-coupled receptor 56-mediated lung metastasis mechanisms in osteosarcoma LM8 cells
Suzuki, N., Hayakawa, E., Nishiura, H., Chen, W., Imasaka, M., Sugimoto, M., Tachibana, T., & Ohmuraya, M. (2026) · Medical Molecular Morphology · doi:10.1007/s00795-026-00467-1
Chokr, S. M., Jimenez, G., Hoang, J., Mai, D., Liang, H. Y., & Cramer, K. S. (2026) · Hearing Research · doi:10.1016/j.heares.2026.109715
Yang, X., Wang, Z., Yang, Y., Chen, S., Qian, X., & Tang, H. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102392
ADGRG1 blockade drives astrocytes into the extracellular matrix to reduce glial scar sizePreprint
Ono, G., Kobayakawa, K., Saiwai, H., Yokota, K., Tamaru, T., Hata, K., Iura, H., Haruta, Y., Kitade, K., Kishikawa, J., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-10546825/v1
Adhesion GPCRs in Kidney: New Insights into Development, Physiology and Disease
Myrzatayeva, A., Singh, A. K., & Engel, F. B. (2026) · Cells · doi:10.3390/cells15181669
Chaudhari, A., & Goyal, S. N. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2026.120231
Yu, X., Yang, F., Shang, W., Cheng, B., Wang, L., Xingwen, X., Chen, M., Tian, Y., & Wang, J. (2026) · Psychological Medicine · doi:10.1017/s0033291726105959
Mechanisms and therapeutic strategies for central and peripheral remyelination
Zhan, J., Jo, J., Cristobal, C. D., Jeong, D. J., Park, H. T., & Lee, H. K. (2026) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2026.102964
Neuroimmune communication: from CNS-resident cell networks to the glioblastoma microenvironment
Li, Y., Zheng, Q., Wang, X., Fu, H., Chen, J., Yao, L., Lin, J., & Wang, R. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.2002570
Metadata
- Authors
- Giera, S., Luo, R., Ying, Y., Ackerman, S. D., Jeong, S.-J., Stoveken, H. M., Folts, C. J., Welsh, C. A., Tall, G. G., Stevens, B., Monk, K. R., & Piao, X.
- Affiliations
- Boston Children's Hospital (US)
- University of Oregon (US)
- University of Michigan (US)
- Oregon Health & Science University (US)
- Corresponding author
- Monk, Kelly R
- Piao, Xianhua
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-05-29
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5980231
- OpenAlex
- W2805257681
- Cited by
- 145
- References
- 76
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 19 · 2023: 10 · 2022: 20 · 2021: 20 · 2020: 19 · 2019: 17 · 2018: 2
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (NS085201, NS085201 (R56), NS087801, NS079445)
- National Multiple Sclerosis Society (FG 2063-A1/2, Harry Weaver Neuroscience Fellowship, RG-1501-02577)
- National Research Foundation of Korea (2015M3C7A1029037)
- Ministry of Science, ICT and Future Planning (KBRI Basic Research program 18-BR-02-02)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tissue transglutaminase, ADGRG1, GPR56, oligodendrocyte precursor cells, myelination, remyelination, demyelination, laminin, extracellular matrix, microglia, OPC proliferation
- MeSH terms
- Oligodendrocyte Precursor Cells, CX3C Chemokine Receptor 1, Remyelination, Protein Glutamine gamma Glutamyltransferase 2, Animals, Cell Differentiation, Cerebellum, Demyelinating Diseases, Female, Humans, Laminin, Male, Oligodendroglia, Transglutaminases, Signal Transduction, Prosencephalon, Microglia, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Lineage, GTP-Binding Proteins, Receptor, Platelet-Derived Growth Factor alpha, Receptors, G-Protein-Coupled, Mice, Neurogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
